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Biomedical subjects

R M Schimpff

Publications and source records attributed to R M Schimpff.

At least 37 records · Page 2Linked to original sources

Variations of growth factors in pregnant women during labor and in newborns at delivery.

To study physiological variations in serum growth factors during peripartal period, we have measured levels of a serum growth-promoting activity (thymidine activity, TA) and radioimmunoassayable somatomedin C (Sm-C) during labor in 39 women who delivered spontaneously (group A), by caesarean section (group B) and by legal abortion (LA) (group C). TA values were higher in the group A than in the group B and C, suggesting an important effect of uterine contractions in TA generation. A major role in Sm-C production seems to be played by the length of gestation since Sm-C concentrations were significantly higher in mothers delivered by caesarean section than in LA women. During labor influence of estrogens and progesterone in growth factor production seems unlikely because of the lack of correlation with TA and Sm-C levels. The lower TA values in placental flow than in the capillary blood of newborn suggest that serum growth factors, measured as TA, are produced by the newborn and do not cross through the placenta. These data suggest that the absolute dependence of the fetus on the mother does not preclude instances of fetal autonomy.

Abortion, Legal↗

Effects of human growth hormone administration on growth rate and growth-stimulating activity of serum, measured by lymphocyte bioassay in hypopituitary children.

The acute effect of human growth hormone (hGH) upon the serum bioassayable growth-stimulating activity was compared to the long-term effects of hGH on growth rate in two groups of hypopituitary patients aged 2-18 years. 12 patients had complete GH deficiency with GH peak below 3.5 ng/ml at two stimulation tests. 15 others, having both GH peaks below 8 ng/ml and at least one above 3.5 ng/ml, were considered as having partial GH deficiency. The growth-stimulating activity of serum was measured by its effect at concentrations 0.03 to 1.25% upon thymidine incorporation into lectin-activated normal human lymphocytes, named thymidine activity (TA). In patients with complete GH deficiency, the pre-treatment TA was positively correlated with the peak response of GH to stimulation tests. The increase of TA after 3-4 days of hGH treatment was positively correlated with the pretreatment TA level, and negatively correlated with the peak GH level. The effect of a 6-12 months therapeutic course of hGH upon the growth rate was positively correlated with the acute increase of TA. No such correlations were found in patients with partial GH deficiency. Many works have discussed the relationship of acute somatomedin responses and long-term clinical results of treatment with hGH in GH-deficient children. The present data, using a highly sensitive bioassay of serum stimulating activity, suggest that the degree of GH deficiency is an important factor to be considered. The response of GH-dependent serum growth factors to acute treatment with hGH could have more predictive value in cases with total lack of growth hormone than in cases of partial deficiency.

Adolescent↗

Effect of bromocriptine treatment on circulating somatomedins in tall adolescents.

Somatomedin and bromocriptine levels were measured before and after 3 months of bromocriptine treatment (5 mg/day) in the sera of 16 tall adolescents with excessive adult height prediction. Somatomedins were measured by RIA for somatomedin C and IgFII and by measuring thymidine incorporation into human lectin-activated lymphocytes. Mean +/- SEM levels of bromocriptine after three months of treatment were 0.61 +/- 0.08 ng/ml. No changes in radioimmunoassayable somatomedin C were observed after bromocriptine intake respectively 1.34 +/- 0.17 U/ml before and 1.4 +/- 0.01 U/ml during treatment. On the opposite a significant decrease of thymidine activity (p less than 0.002) from 1.45 +/- 0.17 U/ml to 1.12 +/- 0.19 U/ml was observed. No changes of IgFII levels were observed in the sera of the 8 patients where they were measured. In order to test a possible direct effect of bromocriptine on peripheral tissues bromocriptine mesylate was added in somatomedin bioassays. Inhibitory effect of bromocriptine in vitro is seen at higher levels (1 microM) compared to the circulating one (1 nM). This study demonstrates that the major effect of bromocriptine which is the acceleration of bone maturation is not related to changes in somatomedin C.

Body Height↗

Effect of the variations of female sex hormones during the menstrual cycle upon serum somatomedin and growth-promoting activity.

Serum growth-promoting activity measured upon lymphocytes, sulfation activity and radioimmunoassayable somatomedin C (Sm-C) levels were measured in sera from women during the menstrual cycle. The data showed that: estradiol, progesterone, LH or FSH added in vitro do not increase the 3H-thymidine uptake into lymphocytes; the serum thymidine activity decreases during the luteal stage of the cycle, and is negatively correlated with the progesterone levels; the sulfation factor and Sm-C levels do not have significant variations during the menstrual cycle, and the GH maximum values are attained during the luteal stage.

Adult↗

Serum thymidine activity and somatomedin-C levels in children and adolescents with Turner's syndrome: effect of chronic estrogen and progestogen replacement therapy.

Turner's syndrome has been used as a model of primary hypogonadism to assess the role of estrogen-progestogen replacement therapy on serum thymidine activity (TA) and somatomedin-C (Sm-C) levels. 33 subjects with gonadal dysgenesis were studied: 10 untreated and 13 treated with estrogen-progestogen combination. In 10 untreated patients serum TA was 1.02 +/- (SEM) 0.04 U/ml and serum Sm-C value was 27.82 +/- 4.14 nmol/l, both similar to those in the age-matched normal children. A positive correlation was found between Sm-C and the bone age (r = 0.891, p less than 0.002). In the 13 treated subjects, the estrogen-progestogen combination as replacement therapy induced a significant increase in Sm-C level (40.52 +/- 4.30 nmol/l, p less than 0.05). No variation was observed for serum thymidine activity between the two groups of subjects.

Adolescent↗

[Effect of serum fractions on the incorporation of tritiated thymidine in activated lymphocytes: I. Human serum from normal adult subjects].

Fractionation of normal human adult serum using Centrisart or gel filtration at neutral pH shows that serum thymidine activity, measured as the ability to stimulate the 3H-thymidine uptake into lectin-activated lymphocytes, is represented by several molecular forms distinct from the endogenous Sm-C. The main thymidine activity is found in the 50-70 K range.

Adult↗

[Effect of serum fractions on the incorporation of tritiated thymidine in activated lymphocytes: II. Comparison between cord blood and the blood of newborn infants].

After serum Sephacryl 300 gel filtration, the major circulating forms of TA in serum are macromolecular. However different patterns are found in cord blood and in the blood of newborns at 24 hr of life. The low values found in cord blood are not due to inhibiting factor(s). TA in serum fractions does not parallel immunoreactive Sm-C levels. The pattern of immunoreactive Sm-C are similar in both cord blood and newborn blood.

Blood Physiological Phenomena↗

Neonatal serum growth-promoting activity measured in human lymphocytes: comparison of cord and capillary blood.

The growth-promoting activity of serum was studied in 47 normal full-term newborns, comparing the effects of cord and of capillary serum upon the 3H-thymidine uptake into activated adult human lymphocytes. At birth the mean +/- SEM (TA) was significantly higher (P less than 0.001) in capillary serum (1.26 +/- 0.08 U/ml) than in cord blood (0.88 +/- 0.05 U/ml), the individual values being significantly correlated. The relatively low values in cord blood do not result from the presence of an inhibitor, nor from the cortisol levels. It may be concluded that study of cord blood is not the best means to measure growth-stimulating factors in newborns.

Blood Specimen Collection↗

Serum growth-promoting activity in human newborns. Relationship of thymidine activity with birth weight and the length of gestation.

Thymidine Activity (TA) was measured by the effect of serum upon incorporation of 3H-thymidine into human lectin-activated lymphocytes in 54 newborns: 32 full-term, 11 pre-term and 11 with intra-uterine growth retardation (IGR). Capillary blood was collected at 0-6 hours, with routine samplings. TA values were lower in preterm (0.476 +/- 0.079 U/ml) than in IGR (0.910 +/- 0.118 U/ml, p less than 0.01) and in full-term neonates (1.237 +/- 0.60, p less than 0.001), and also in IGR newborns than in newborns of normal weight (p less than 0.025). In preterm neonates TA was significantly correlated with gestational age (r = 0.715, p less than 0.02), but no such correlation existed in IRG and full-term neonates. When TA values were plotted against birth weight, a correlation was found in preterm (r = 0.715, p less than 0.02) and in IGR newborns (r = 0.714, p less than 0.02), but not in full-term neonates. Longitudinal study up to 21 days did not show significant changes in full-term newborns, while in preterm and IGR neonates TA increased progressively to reach normal values at the 21st day. The correlations observed in newborns between TA, birth weight and gestational age, and the postnatal normalization in newborns with low birth weight, show that TA directly reflects the nutritional state of the fetus.

Birth Weight↗

Effects of gonadotrophin-induced elevation of serum testosterone upon somatomedin C levels and serum thymidine activity in children.

3H-thymidine uptake into lectin-activated human lymphocytes allows to measure a growth-stimulating activity of serum, the thymidine activity (TA), which is GH dependent in vivo and related to somatomedins (Sm). In this work, it is shown: that addition of human chorionic gonadotrophin (HCG) or testosterone in vitro does not increase the 3H-thymidine uptake into lymphocytes; that the gonadotrophin-induced elevation of testosterone in children is accompanied by a significant increase of TA and, at a lesser degree, of Sm C; that these two increases are significantly correlated, and that the age-related variation of TA and Sm C after HCG stimulation test are not parallel.

Adolescent↗

Bioassay of growth-stimulating activity of serum: comparison of lymphocyte and cartilage assays in normal and growth hormone-deficient children.

The somatomedin and/or growth-stimulating activity of serum from hypopituitary children and short children with normal growth hormone (GH) response to stimulation tests were studied using different bioassays: thymidine incorporation into human activated lymphocytes; sulfate incorporation into chick embryo cartilage; and simultaneous thymidine uptake into the same cartilages. The results showed that lymphocyte assay is highly sensitive to small amounts of serum and is GH-dependent in children with low GH secretion. On the contrary, the cartilage assays need higher serum concentration and their GH-dependence appears only in subjects with normal or low-normal GH secretion. The lack of correlation between the results of the three bioassays suggests that they measure both somatomedins and different serum factors involved in the regulation of growth.

Adolescent↗

Serum growth-promoting activity measured as [3H]thymidine incorporation into human activated lymphocytes and serum transferrin levels in newborns and mothers.

Serum growth-promoting activity measured as [3H]thymidine incorporation into human activated lymphocytes and serum transferrin levels were measured during the perinatal period in newborns and mothers. Both thymidine activity (TA) and transferrin levels were significantly increased at the time of delivery in mothers compared to control women, and there was a progressive return to control levels in the first 5 postpartum days. A significant correlation was found between TA and placental weight. In the newborns, TA was low in cord blood after vaginal delivery but not in the cord blood from babies born by cesarean section. In premature newborns, TA was lower than in full term newborns. In all newborns during the first 24 postnatal hours, there was an increase in TA with levels rising above adult control values: levels in cord blood were positively correlated with birth weight but not with thymidine activity. These data afford complementary insights into the humoral controls of growth in newborn infants.

Adult↗

Serum thymidine activity and insulin-like growth factors in the neonatal period.

Growth-promoting activity measured as [3H] thymidine incorporation into lectin-activated lymphocytes was determined simultaneously with radioimmunoassayable IGF I and IGF II in cord and capillary blood collected from human neonates 30 min and 24 h after birth. All the parameters studied in cord blood were lower than in normal adults. During the early postnatal period, IGF I decreased and IGF II remained unchanged, but thymidine activity increased above the normal adult level. The differences between the values found in cord blood and in capillary blood collected within the first 1/2 h after birth agree with a production of growth factors by the infant. All these growth factors may play a role in foetal growth, as suggested by their correlation with birth weight. Finally, factors other than IGFs contributing to thymidine activity may play a role in neonatal growth since they are higher in newborns than in adults.

Age Factors↗

Growth-promoting activity of serum throughout pregnancy and at delivery: evaluation by three different bioassays.

Somatomedin evolution has been studied by employing three different bioassays in 181 pregnant women from the 7th week of gestation to delivery and in 18 women during the course of labor. In 105 additional mothers of full-term or pre-term neonates a significant increase of a serum growth-promoting activity (thymidine activity) was observed at delivery, as compared to nonpregnant controls, with a progressive return to normal levels in the post-partum period. Different results were found according to the assay method used, suggesting the multiplicity of growth factors and specific adaptations related to the stages of pregnancy.

Biological Assay↗

Somatomedin, transferrin and amino-acids in serum following injection of human growth hormone in children with growth disease.

17 children with growth retardation (12 with idiopathic hypopituitary dwarfism, 2 with craniopharyngioma and 3 constitutionally short) were studied for three days following a single intramuscular injection of human growth hormone. Somatomedin activity was bioassayed using both sulphate incorporation into chick embryo cartilage and thymidine uptake by human lectin-activated lymphocytes. In hypopituitary patients it showed a significant response, maximal 24 hours after the injection, and significantly correlated for the two bioassays. The aminoacid content of the incubation medium used for thymidine bioassay appeared as an important factor: both glutamine and nonessential aminoacids are required to obtain significant stimulation by low serum concentrations, thus increasing the sensitivity of the assay but reducing the differences between normal and hypopituitary sera. Transferrin levels in serum were significantly lower in hypopituitary dwarfs. They did not rise in the three days following hGH. Aminoacid levels were lower in idiopathic GH deficient patients than in other groups, and did not show short term increase in the fasting samples collected after hGH administration.

Adolescent↗

Plasma growth-promoting activity measured as thymidine activity in constitutionally short children.

Growth-stimulating activity of plasma was measured, both as thymidine activity using a lymphocyte bioassay and as sulfation activity using a cartilage bioassay, in 72 constitutionally short children aged 1-6 years and 38 age-matched controls. Plasma transferrin was also measured. No significant differences were found between the two groups. However, short children aged 1-3 years did not have higher thymidine activity than children aged 4-10 years, whereas in normals the thymidine activity was significantly higher in the first years of life. Thymidine activity was lower in female than in male constitutionally short children.

Adolescent↗

Growth hormone dependency of the effect of human serum on thymidine uptake by lectin-activated human lymphocytes.

This study of the effect of serum dialysis on thymidine incorporation into lectin-activated blood lymphocytes cultured in vitro showed that (1) after serum dialysis 3H-thymidine incorporation is very low or absent; (2) the addition of L-glutamine to dialyzed sera leads to recovery of 18% of 3H-thymidine uptake, and (3) addition of L-glutamine reduces the difference in the stimulating effects of acromegalic and hypopituitary sera observed before dialysis in a medium free of L-glutamine. Since the plasma level of glutamine is increased in acromegalics and reduced in hypopituitary patients, it is suggested that this amino acid acts as a growth hormone dependent factor or cofactor in the regulation of cell growth.

Acromegaly↗

[Stimulating action of human serum on the incorporation of tritiated thymidine in human lymphocytes activated by lectins: demonstration of the GH-dependency and its limitations].

Using thymidine uptake by activated human lymphocytes to measure the growth-stimulating activity of human serum, the authors demonstrate that thymidine activity was significantly correlated (p less than 0.001) with GH levels. r = 0.729 when GH values are below 3.5 ng/ml, r = 0.509 when GH values are below 8 ng/ml and r = 0.337 for all of the patients. Low levels of GH are sufficient for the generation of this activity.

Adolescent↗